Division of Disease Control and Health Protection

CDC PROVIDES NOTICE OF THE AVAILABILITY OF HEPATITIS B VACCINE WHICH DOES NOT CONTAIN THIMEROSAL AS A PRESERVATIVE

The Centers for Disease Control and Prevention (CDC) provided a notice to readers, "Availability of Hepatitis B Vaccine That Does Not Contain Thimerosal as a Preservative," in the September 10, 1999 issue of the MMWR. The authors state that "the availability of hepatitis B vaccine that does not contain thimerosal as a preservative should alert medical facilities to review their policies to ensure the vaccination of newborns as recommended by the Advisory Committee on Immunization Practices, AAFP, and AAP." "Routine hepatitis B vaccination policies for all newborn infants should be reintroduced immediately in hospitals in which these policies and practices have been discontinued."

Because the availability of such vaccine should be of interest to all immunization providers, the entire article is reprinted below.

On August 27, 1999, Merck Vaccine Division* (Merck & Co., Inc., West Point, Pennsylvania) received approval from the Food and Drug Administration (FDA) of a supplement to Merck's license application to include the manufacture of single-antigen preservative-free hepatitis B vaccine (Recombivax HB, Pediatric); distribution is expected to begin September 13, 1999. In addition, SmithKline Beecham Biologicals (SmithKline Beecham, Philadelphia, Pennsylvania), expects to make single-antigen preservative-free hepatitis B vaccine (Engerix-B, Pediatric) available in the near future. Further product information will be provided when it becomes available. Product packaging and labels will indicate that these vaccines do not contain preservative.

To prevent shortages because of limited supplies of single-antigen hepatitis B vaccines that do not contain thimerosal as a preservative and to assure prevention of perinatal and early childhood hepatitis B virus (HBV) infection during the transition when both vaccines that contain and do not contain thimerosal as a preservative are available, the following three steps should be taken:

1. Newborn infants. The priority for use of single-antigen hepatitis B vaccines that do not contain thimerosal as a preservative should be to vaccinate newborn infants. Routine hepatitis B vaccination policies for all newborn infants should be reintroduced immediately in hospitals in which these policies and practices have been discontinued. All hospitals should ensure that newborn infants of hepatitis B surface antigen (HBsAg)-positive mothers and of mothers whose HbsAg status is unknown receive their first dose of hepatitis B vaccine within 12 hours of birth. If hepatitis B vaccine that does not contain thimerosal as a preservative is not available, then thimerosal preservative-containing vaccine should be used for these infants.

2. Infants aged less than 6 months. When available, hepatitis B vaccines that do not contain thimerosal as a preservative should be used to vaccinate infants aged less than 6 months (single-antigen hepatitis B vaccine for infants aged less than 6 weeks and either single-antigen or combination products for infants aged greater than or equal to 6 weeks). Infants in groups at high risk for perinatal and early childhood HBV infections should complete the three-dose hepatitis B vaccine series by age 6 months. When vaccines that do not contain thimerosal as a preservative are not available, these groups should be vaccinated with thimerosal preservative-containing vaccine. For infants born to HBsAg-negative mothers and who are not in high-risk groups, existing recommendations should be used for administering thimerosal preservative-containing hepatitis B vaccines if vaccine that does not contain thimerosal as a preservative is not available (1-4). These groups should complete the three-dose hepatitis B vaccine series by age 18 months.

3. Children aged greater than or equal to 6 months, adolescents, and adults. Thimerosal preservative-containing hepatitis B vaccines can continue to be used for vaccinating children aged greater than or equal to 6 months, adolescents, and adults as is recommended (1-6).

Reported by: National Center for Infectious Diseases; National Immunization Program; Agency for Toxic Substances and Disease Registry; National Center for Environmental Health, CDC.

Editorial Note: On July 8, 1999, the American Academy of Pediatrics (AAP) and the Public Health Service (PHS) released a joint statement about thimerosal in vaccines, and the American Academy of Family Physicians (AAFP) released a comparable statement (1-3). Thimerosal is a mercury-containing preservative that has been used as an additive to biologics and vaccines since the 1930s because it is effective in preventing bacterial and fungal contamination, particularly in open multidose containers.

Vaccine manufacturers, FDA, and other PHS agencies are working together to replace expeditiously thimerosal preservative-containing vaccines whenever possible with vaccines that do not contain thimerosal as a preservative while ensuring maintenance of high vaccination coverage levels and prevention of disease.

Previous recommendations for using thimerosal-containing vaccines indicated that clinicians and parents could take advantage of the flexibility in the immunization schedule to delay hepatitis B vaccination from birth until age 2-6 months for infants born to mothers who are HBsAg negative (1-4). No changes were made in recommendations for immunization at birth of infants of HBsAg-positive mothers or infants of mothers with an unknown HBsAg status.

After the joint AAP/PHS statement on thimerosal, the AAP and CDC provided additional implementation guidance (3,4). CDC guidance included hepatitis B vaccination should be continued at birth for infants born to HBsAg-negative mothers belonging to populations or groups that have a high risk for early childhood HBV infection, including Asian/Pacific Islanders, immigrant populations from countries in which HBV infection is of high or intermediate endemicity (7), and households with persons with chronic HBV infection. To ensure the prevention of perinatal HBV transmission, hospitals should continue policies to vaccinate all infants at birth until procedures are in place to guarantee that 1) the HBsAg status of every pregnant woman is reviewed at delivery, 2) appropriate passive-active immunoprophylaxis (hepatitis B immune globulin and hepatitis B vaccine) is provided for infants of HBsAg-positive women within 12 hours of birth, and 3) appropriate active immunoprophylaxis (hepatitis B vaccine) is provided for infants of women with an unknown HBsAg status.

After the statements on thimerosal in vaccines were published, changes occurred in newborn hepatitis B vaccination policies and practices in some hospitals, including unintended changes affecting immunization of infants at risk for perinatal HBV transmission. In August 1999, state and territorial health department hepatitis coordinators conducted surveys of selected birthing hospitals in their project areas. Of 977 hospitals surveyed in 48 project areas, 773 (79%) were aware of the joint AAP/PHS statement on thimerosal. Of 574 hospitals that were aware of the statement and had existing policies or standing orders to vaccinate all newborns, 262 (46%) reported a policy change to no longer routinely vaccinate newborns of HBsAg-negative mothers. In addition, 52 (9%) reported they no longer routinely vaccinate any newborn (CDC, unpublished data, 1999). Such a policy usually requires a physician's order to vaccinate infants of HBsAg-positive mothers and infants of mothers whose HBsAg status is unknown. CDC also has received anecdotal reports of hospitals in which policies were changed, and infants born to HBsAg-positive mothers and infants born to mothers with unknown HBsAg status were not vaccinated within 12 hours of birth (CDC, unpublished data,1999). Chronic HBV infection develops in approximately 90% of infants infected perinatally; among chronically infected infants, the risk for premature death from HBV-related liver cancer or cirrhosis is approximately 25% (8). The availability of hepatitis B vaccine that does not contain thimerosal as a preservative should alert medical facilities to review their policies to ensure the vaccination of newborns as recommended by the Advisory Committee on Immunization Practices, AAFP, and AAP.

References

1. CDC. Thimerosal in vaccines: a joint statement of the American Academy of Pediatrics and the Public Health Service. MMWR 1999;48:563-5.

2. American Academy of Pediatrics. Thimerosal in vaccines: an interim report to clinicians. AAP News 1999;15:10-2.

3. American Academy of Family Physicians. Policy statement of the American Academy of Family Physicians on thimerosal in vaccines, July 8, 1999. Accessed September 3, 1999.

4. CDC. Implementation guidance for immunization grantees during the transition period to vaccines without thimerosal, July 14, 1999.

Accessed September 3, 1999.

5. Advisory Committee on Immunization Practices. Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination. MMWR 1991;40(no. RR-13).

6. CDC. Update: recommendations to prevent hepatitis B virus transmission--United States. MMWR 1999;48:33-4.

7. CDC. Health information for international travel 1999-2000. Atlanta, Georgia: US Department of Health and Human Services, 1999:98-102.

8. Margolis HS, Coleman PJ, Brown RE, Mast EE, Sheingold SH, Arevalo JA. Prevention of hepatitis B virus transmission by immunization: an economic analysis of current recommendations. JAMA 1995;274:1201-8.

* Use of trade names and commercial sources is for

identification only and does not imply endorsement by CDC

…It is not my purpose to more than direct your attention to certain features of this report which to me are particularly interesting from a business man’s point of view and which seem to bear especially upon the State-wide influence which the Board has induced during the past twenty-years and from which great good has resulted to the people both educationally and practically.

It is a well known fact that prior to the great epidemic of yellow fever in 1888 the increase in the State’s population from immigration was almost inappreciable compared with the gain since the period mentioned. It is within the memory of even our younger people that as each summer came there was talk of yellow fever, its probability of occurrence and the point where it would first make its appearance. This periodic agitation of a subject which vitally interested not only the physical life of the citizen, but his business existence as well, brought about conditions which yearly disturbed home comfort and retarded the coming of people into the state, besides restricting investment capital, so necessary to develop many important industries and avenues of commerce which held our flattering returns. People were scary, and naturally so in placing their money where health conditions were so uncertain and where an epidemic of yellow fever depressed values to a degree that it would take years of exemption to recover from…

Compare the condition existing in the State in 1888 with an epidemic of yellow fever in Jacksonville, and the conditions which prevailed in 1905 with an epidemic of the same disease in Pensacola, Fla. In the former instance panic prevailed; every man’s hand was raised against his neighbor of adjoining counties, under a false supposition of protection against an unseen enemy; commerce was strangled and stagnation of business followed. In 1905 – in the latter instance – without a ten-mile area around Pensacola, travel within the State was undisturbed. Business followed its usual methods and there was no panic, no excitement, no hysteria of even those most skeptical of the ability of the State Board of Health to cope with the situation and confine the disease to one point in the State…

These facts are mentioned to you, not in a boastful way, but to emphasize the growth of confidence on the part of the people in an institution which the people themselves in their wisdom had provided for in the Constitutional Convention of 1885…

Is it unreasonable, therefore, to argue or to maintain that the part played in the wonderful development of Florida since 1888 has not been due very largely to a confidence in the safety of living in the State, which…has been inspired by the work which the State Board of Health has done along health lines and… is still earnestly engaged in?…I do not say or pretend to assert that the State Board of Health has been the only factor in the strides which Florida has made towards financial development in the past twenty years, but I do maintain without fear of successful contradiction, that the Board has contributed a large share to the success which the State now enjoys, and it will be recognized in the future, if not already so considered, as an investment on the part of the people which should be allowed the greatest latitude of administration.